Open Access Open Badges Research article

Increased incidence of pregnancy complications in women who later develop scleroderma: a case control study

Linda van Wyk1*, Jacolien van der Marel1, Annemie JM Schuerwegh2, Anne A Schouffoer2, Alexandre E Voskuyl3, Tom WJ Huizinga2, Diana W Bianchi4 and Sicco A Scherjon1

  • * Corresponding author: Linda van Wyk

  • † Equal contributors

Author Affiliations

1 Department of Obstetrics, Leiden University Medical Centre, Albinusdreef 2, 2333ZA Leiden, PO BOX 9600, 2300 RC Leiden, The Netherlands

2 Department of Rheumatology, Leiden University Medical Centre, Albinusdreef 2, 2333ZA Leiden, PO BOX 9600, 2300 RC Leiden, The Netherlands

3 Department of Rheumatology, VU University Medical Centre, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands

4 Department of Pediatrics, Floating Hospital for Children at Tufts Medical Centre, 755 Washington Street, Boston, MA 02111, USA

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Arthritis Research & Therapy 2011, 13:R183  doi:10.1186/ar3510

Published: 4 November 2011



Studies have shown that fetal progenitor cells persist in maternal blood or bone marrow for more than 30 years after delivery. Increased trafficking of fetal cells occurs during pregnancy complications, such as hypertension, preeclampsia, miscarriage and intra-uterine growth restriction (IUGR). Women with these pregnancy complications are significantly more often HLA-class II compatible with their spouses. Women who later develop scleroderma also give birth to an HLA-class II child more often. From these prior studies we hypothesized that preeclampsia and other pregnancy complications could be associated with increased levels of fetal cell trafficking, and later be involved in the development of scleroderma.


This study was a retrospective multi-centre matched case-control study. One-hundred-and-three women with systemic sclerosis (SSc) and 103 women with no history of SSc or other autoimmune disease were given a questionnaire regarding complications during pregnancy, such as hypertension, intra-uterine growth restriction (IUGR) and miscarriage. Conditional logistic regression analysis was used to assess associations.


We found a statistically significantly increased incidence of having had a pregnancy history of hypertension or a fetus with IUGR in women who subsequently developed SSc compared to healthy controls. We found an odds ratio of 2.6 (95% confidence interval (CI): 1.1 to 4.6) for hypertensive complications during pregnancy and an odds ratio of 3.9 (95% CI: 1.2 to 12.3) for intra-uterine growth restriction for women with SSc compared to healthy controls.


This is the first study to show an association between hypertensive complications during pregnancy or IUGR and the development of SSc at a later age. We speculate that the pregnancy abnormalities may have resulted in increased fetomaternal trafficking, which may have played a role in the increased incidence of SSc. Further studies are indicated to examine this putative relationship.

Pregnancy; Chimerism; Systemic sclerosis; Hypertension; Pre-eclampsia; Intra-uterine growth restriction